Interaction of amines and aminergic blocking agents with blood glucose regulation. I. β-adrenergic blockade

Abstract

The influence of specific β-adrenergic blockade on blood glucose hemeostasis in vivo and glucose utilization in vitro was investigated in mice. Treatment of normal, freely fed mice with L-propranolol induced a moderate hyperglycaemia, an increase of muscle glycogen, and a slight decrease of liver glycogen. The D-isomer had no effect. L-Propranolol reduced the plasma insulin level by about 50%. L- and D-alprenolol, and D-propranolol had no influence on the plasma insulin level. Pretreatment with L-propranolol abolished catecholamine-induced hyperglycaemia, increased muscle glycogen, and decreased hepatic glycogen. D-Propranolol reduced the blood glucose level of alloxan-diabetic animals and potentiated insulin-induced hypoglycaemia in both normal and alloxan-diabetic mice. Incubation of liver, muscle, and adipose tissue in vitro with L- and D-propranolol, respectively (D-propranolol as control) gave the following results on glucose utilization: L-propanolol induced an increased 14CO 2-production and 14C-incorporation into glycogen from 14C-glucose in muscle tissue. Also the total glycogen content of L-propranolol-treated muscle tissue was higher than in control tissue. These effects by L-propranolol were also seen in the presence of L-adrenaline and L-adrenaline + insulin. 14C-Incorporation into adipose tissue glycogen was increased by L-propranolol in the presence of L-adrenaline and L-adrenaline + insulin. L-Propranolol increased glucose utilization by adipose tissue in the presence of large amounts of L-adrenaline. Liver glycogen content was slightly higher as compared to control tissue after incubation with L-propranolol in the presence of large amounts of L-adrenaline or L-adrenaline + insulin. It is suggested that the blood glucose level in normal mice is to some extent controlled by β-adrenergic activity. Depending on the metabolic condition of the animal, specific β-adrenergic blockade may cause either: (1) a hyperglycaemic effect by an inhibitory action on insulin secretion and an augmented glucose production by the liver (freely fed animals); (2) a hypoglycaemic effect by means of an increased glucose utilization and a glycogen preserving effect in muscle and adipose tissue (e.g. during starvation, diabetes, and insulin-induced hypoglycaemia).